Neural Response to Social Exclusion Moderates the Link Between Adolescent Anxiety Symptoms and Substance Use

Background Substance use (SU) typically increases from middle to late adolescence. Anxiety is one factor associated with greater SU, although variability in who uses substances remains. Some models suggest that brain-based susceptibility markers could reveal which adolescents are at a higher risk for psychopathology, but it is unknown whether these individual differences attenuate or accentuate the association between anxiety and elevated SU even if normative. This study addressed this gap by testing whether neural response to social exclusion moderates the association between anxiety symptoms and increased SU from middle to late adolescence. Methods Participants were 181 Mexican-origin adolescents (48% female; 16–17 years old) who completed a social exclusion task during a functional magnetic resonance imaging scan and filled out questionnaires about their SU and anxiety symptoms. Analyses focused on neural response to social exclusion versus inclusion within 3 regions of interest and change in SU across 2 years. Results Dorsal anterior cingulate cortex response to social exclusion, but not subgenual anterior cingulate cortex or anterior insula, moderated the relation between anxiety symptoms and SU, such that higher anxiety symptoms predicted a greater relative increase in SU only for those youth with a lower dorsal anterior cingulate cortex response to exclusion. Conclusions Blunted dorsal anterior cingulate cortex response to social exclusion may serve as a neural susceptibility marker of altered conflict monitoring or emotion regulation in middle adolescence that, in combination with high levels of anxious feelings, elevates the risk for onset of and/or increased SU by late adolescence. These findings have implications for designing targeted interventions to mitigate SU among adolescents.